Studies suggest that repetitive Transcranial Magnetic Stimulation (rTMS) is a potential therapy for Parkinson's Disease (PD). rTMS generates changes in cortical excitability that extend beyond the time of the stimulation. However, the mechanisms for these changes are not well understood yet. The long-term objectives of this proposal are to: (1) understand the mechanisms by which rTMS modulates cortical excitability, (2) examine the time course of rTMS effects on cortical excitability, (3) study how motor function is affected by changes in cortical excitability, (4) translate our knowledge of the basic mechanisms of rTMS into therapy for PD. The specific aims of this research are to systematically investigate how rTMS parameters (frequency, intensity, train duration, and intertrain interval) and how their interactions affect cortical excitability and motor function in patients with PD and normal controls. The study will be a 4-factor, blocked, mixed factorial design (2 within-subject and 2 between-subject variables, blocked by PD), which will allow us to determine how rTMS with different combinations of frequency (1 or 10 Hz), intensity (90% or 120% of the rest motor threshold), train length (20 stimuli or 40 stimuli per train), and intertrain interval (5 s or 30 s) modulate cortical excitability within the PD and normal control populations. We will assess cortical excitability by recruitment curves of motor evoked potentials, cortical silent periods and intracortical inhibition. We will assess motor function by alternate finger tapping. The time courses of the neuromodulatory effects of rTMS will be assessed at 20 minutes intervals for one hour after rTMS is administered. We anticipate rTMS will modulate cortical excitability, and motor function differentially in the PD and normal control populations. The results will provide us with vital information that will allow us to further develop rTMS as a noninvasive therapeutic modality for PD.